PB2249: ATYPICAL CHRONIC MYELOID LEUKEMIA (ACML) AND AUTOIMMUNE DISEASE: REPORT OF TWO CASES.
Authors: Caterina Tatarelli, Annapaola Leporace, Federica Lubrano Lobianco, Elena Antonini, Arianna DI Napoli, Agostino Tafuri
Journal: HemaSphere (2023)

Topic: 16. Myeloproliferative neoplasms - Clinical Background: Autoimmune disorders (AD) can promote immune-related or inflammation driven tumorigenesis leading rarely to myeloproliferative neoplasms.Atypical chronic myeloid leukemia(aCML) is a rare BCR-ABL1-negative clonal disorder belonging to the myelodysplastic/myeloproliferative group with a very low incidence and a poor prognosis.No established standards of care exist for its treatment. Aims: We report for the first time two cases of aCML associated with previous diagnosis of autoimmune disease. Methods: The first case is a 56years old woman,with a history of rheumatoid artritis diagnosed in 2018, treated with metotrexate (MTX) until May 2022.The patient was admitted in July 2022 because of increasing fatigue. Mild spleen (12.8 cm) and hyperleukocytosis with White Blood Cell (WBC) 43 X 109/L, and anemia with hemoglobin (Hb) of 85 g/L and normal Platelets (PLT) count 173 X 109/L was observed. Manual count:64% Neutrophiles,12%Lymphocytes,13%metamyelocytes, 5%myelocytes, 2%promyelocytes;3%Erythroblasts, 3%monocytes,1%basophilic granulocytes,2% Blasts. Bone Marrow Aspirate (BMA)showed hypercellular marrow,with myeloid hyperplasia and trilineage displasia.Bone marrow (BM) biopsy was hypercellular (95%),increase of the hypersegmented granulocytic proliferation and degranulocytic dysplasia,erythroid dysplasia, and grade 1 Fibrosis (MF-1),Blasts 5%.Cytogenetic revealed a normal karyotype.PCR for BCR-ABL1 and JAK-2 was negative.Next generation sequencing(NGS)revealed mutation of SRSF2(VAF40%);ASXL-1(VAF47%), RUNX1(VAF46%).The patient was diagnosed with aCML and treated with low dose Hydroxyurea(HU) at a dosage of 1.5/2 gr a week.She needed a transfusion once a month. Currently, her blood count (BC) is Hb 94 g/L, WBC 14.6 X 109/L, PLT 146 X 109/L.HLA typing is ongoing to search for potential donors for hematopoietic stem cell transplantation.The second case is a 72-year-old man presented with anemia and hyperleucocytosis in 2019.He had a history of Psoriatric artritis diagnosed in 2005 treated with MTX for four months.He presented with mild splenomegaly (13 cm).His complete BC showed Hb of 87 g/L,WBC of 22.3 X 109/L and normal PLT 140 X 109/L. PB showed hyperleucocytosis with myeloid precursors,disgranulopoiesis with 30% neutrophils,29% lymphocytes,1% eosinophils,2% monocytes,4% basophils,24% metamyelocytes,20% myelocytes, 4% erythroblasts,5% blasts.BMA was hypercellular with marked trinileage dysplasia and erytroblastic hypoplasia with 1 % blasts.BM biopsy was hypercellular with MF-1.Karyotype showed 46 XY.PCR tests for BCR-ABL1 and JAK2 were also negative.NGS revealed mutations in ASXL1(VAF48%), CUX1(VAF49%), FLT3 (VAF7%),SETBP1(VAF47%),SRSF2 (VAF 48%).High BC transfusion was needed also due to diagnosis of angiodysplasia of the small bowel.The patient was diagnosed with aCML and treated with a dose of HU at a 1.5g/week.Currently his BC count is Hb 85 g/L, WBC of 22.3 X 109/L, PLT of 38 X 109/L and receives HU at a dosage of 7g/week. Results: Both patients were diagnosed with aCML,carrying both a SRSF2 mutation. Both received a low dose of HU and had a diagnosis of autoimmune disease treated previously with MTX. Summary/Conclusion: aCML is a rare disease whose diagnosis has become easier with the application of NGS technologies, also with the aim to find actionable mutations. Patients with AD have an increased risk of developing myeloid diseases. Immune-related driven tumorigenesis and alternatively the treatments given to patients with AD might play a role in the development of myeloproliferative neoplasms. E-Mail Address: [email protected] Keywords: Myeloproliferative disorder, Chronic myeloid leukemia, Autoimmunity